ThenumberofindividualswithOpioidUseDisorder(OUD)continuestorisewithmorethan2.5million affected,alongwithsubstantialmorbidityandmortality.Severaleffectivemedicationsareavailabletotreat OUDwithbuprenorphinebecomingtheprimarymedicationusedinthecommunity.Buprenorphineiseffective forapproximately50-70%ofpatientsandbetterresultsareachievedwiththelongerdurationoftreatment. However,theprospectoflong-termopioidmaintenanceisnotacceptabletosomepatientsandtheyeventually requesttostoptreatmentordiscontinueitontheirown.Asmanypatientswhohadgoodtreatmentresponse desiretodiscontinuethemedicationthereisaneedtocollectevidenceaboutthebeststrategytoaccomplish that.Opioidreceptorantagonistnaltrexoneisapprovedforrelapsepreventionfollowingdetoxificationoff opioids.Naltrexonecanbestartedasafirst-linetreatmentfollowingdiscontinuationoffillicitopioidsanditmay alsobeusedasanadjunctforpatientswhowishtodiscontinuebuprenorphinemaintenanceandwouldliketo beprotectedfromrelapse.Weproposeanopen-labelrandomizedoutpatienttrialtoevaluatefeasibilityand efficacyofrapidBUPdiscontinuationfollowedbybriefcourseoftreatmentwithlong-actingnaltrexone(XR- NTX)andtocompareittothestandardmethodofgradualBUPtaper. IndividualswithOUD(N=55)whohavesuccessfullycompletedatleast6monthsofbuprenorphinetreatment anddonotwishtoremaininalong-termbuprenorphinemaintenanceprogramwillberecruited.Thefirstphase includesa4-weekperiodofstabilizationonbuprenorphine4-8mgattheresearchclinictoassurethatpatients arestable,compliant,andfreefromillicitopioids.Participantsthatmeettheabovecriteriawillberandomized 1:1to:1)buprenorphinediscontinuationandoutpatienttransitiontoXR-NTXwith3monthlyinjections,or2) buprenorphinediscontinuationusingagradual,5-weeklongtaper.Inbothgroupsparticipantswillreceive weeklyrelapsepreventiontherapyandwillbemonitoredforthedurationofthetrial,whichis25weekspost randomization.Theprimaryoutcomewillbethepercentofpatientssuccessfullytransitionedoffbuprenorphine andabstinentfromanyopioidsatthe25-weektrialendpoint.Secondaryoutcomeswillincludemeasuresof opioidwithdrawal,mood,anxietyandsleepproblems,abstinencefromothersubstances,timetorelapseor dropout,andadverseeffects.Wehypothesizethatmorepatientswillsuccessfullydiscontinuebuprenorphinein thegroupthatreceivedXR-NTX.Thisproposedexploratorytrialwillbeabletoinformthedesignoffuture researchandclinicalwork.ApositivesignalthattransitionfrommaintenancebuprenorphinetoXR-NTXis feasibleandpreventsrelapsewouldencouragealargertrialtoreplicateandperhapsextendtomultiple communitybasedtreatmentsettings.Afeasible,well-tolerated,andeffectivemethodofhelpingpatients wishingtodiscontinuetreatmentwithBUPhasthepotentialtoexpandthepopulationofopioid-dependent individualsbenefittingfromtreatment.